Antilymphocyte antibodies (ALA) have been found in patients with systemic lupus erythematosus (SLE) and a significant percentage of both their blood and non-blood relatives. These antibodies have also been implicated in the defect in immunoregulation found in SLE patients. This project is designed to gain further information on the relationship between ALA and disease activity in SLE families, the mechanisms of their production and their effect on monocyte and lymphocyte function. The correlation between disease activity and subtypes of ALA with specificity for major histocompatibility (MHC) antigenic structures, beta2 microglobulin (beta2-mu), antigens expressed on brain cells and on proliferating lymphocytes will be determined in a longitudinal study of SLE families. Antibodies with these specificities will be isolated by absorption, absorption-elution, or affinity column chromatography, and examined for their effect on the ability of monocytes and T and B lymphocytes to perform in in vitro tests. These tests will include mitogen stimulation, mixed leukocyte reaction (MLR) and immunoglobulin production. The effects of ALA will be compared to those of xenoantibodies with similar specificities. We will also continue to define the role of prostaglandin E2 (PGE2) in feedback control of monocytes and lymphocyte function. Special emphasis will be placed on the mechanism behind the excessive in vitro PGE2 production by monocytes we have found in patients with Hodgkin's disease, SLE, and rheumatoid arthritis (RA). The interplay between PGE2 production and ALA effects will be examined as well as the sensitivity of monocytes and lymphocytes to inhibition by PGE2.